A miRNA-HERC4 pathway promotes breast tumorigenesis by inactivating tumor suppressor LATS1.

The E3 ligase HERC4 is overexpressed in human breast cancer and its expression levels correlated with the prognosis of breast cancer patients. However, the roles of HERC4 in mammary tumorigenesis remain unclear. Here we demonstrate that the knockdown of HERC4 in human breast cancer cells dramatically suppressed their proliferation, survival, migration, and tumor growth in vivo, while the overexpression of HERC4 promoted their aggressive tumorigenic activities. HERC4 is a new E3 ligase for the tumor suppressor LATS1 and destabilizes LATS1 by promoting the ubiquitination of LATS1. miRNA-136-5p and miRNA-1285-5p, expression of which is decreased in human breast cancers and is inversely correlated with the prognosis of breast cancer patients, are directly involved in suppressing the expression of HERC4. In summary, we discover a miRNA-HERC4-LATS1 pathway that plays important roles in the pathogenesis of breast cancer and represents new therapeutic targets for human breast cancer

The Progress, Challenges, and Perspectives of Directed Greybox Fuzzing

Most greybox fuzzing tools are coverage-guided as code coverage is strongly correlated with bug coverage. However, since most covered codes may not contain bugs, blindly extending code coverage is less efficient, especially for corner cases. Unlike coverage-guided greybox fuzzers who extend code coverage in an undirected manner, a directed greybox fuzzer spends most of its time allocation on reaching specific targets (e.g., the bug-prone zone) without wasting resources stressing unrelated parts. Thus, directed greybox fuzzing (DGF) is particularly suitable for scenarios such as patch testing, bug reproduction, and specialist bug hunting. This paper studies DGF from a broader view, which takes into account not only the location-directed type that targets specific code parts, but also the behaviour-directed type that aims to expose abnormal program behaviours. Herein, the first in-depth study of DGF is made based on the investigation of 32 state-of-the-art fuzzers (78% were published after 2019) that are closely related to DGF. A thorough assessment of the collected tools is conducted so as to systemise recent progress in this field. Finally, it summarises the challenges and provides perspectives for future research.Comment: 16 pages, 4 figure

IC-integrated flexible shear-stress sensor skin

This paper reports the successful development of the first IC-integrated flexible MEMS shear-stress sensor skin. The sensor skin is 1 cm wide, 2 cm long, and 70 /spl mu/m thick. It contains 16 shear-stress sensors, which are arranged in a 1-D array, with on-skin sensor bias, signal-conditioning, and multiplexing circuitry. We further demonstrated the application of the sensor skin by packaging it on a semicylindrical aluminum block and testing it in a subsonic wind tunnel. In our experiment, the sensor skin has successfully identified both the leading-edge flow separation and stagnation points with the on-skin circuitry. The integration of IC with MEMS sensor skin has significantly simplified implementation procedures and improved system reliability

Parylene membrane slot filter for the capture, analysis and culture of viable circulating tumor cells

This paper presents a method of capturing viable circulating tumor cells (CTC) from human whole blood using constant-pressure-driven filtration through a specially designed parylene-C membrane “slot” filter. More than 90% viable cancer cells could be recovered from whole blood using the slot filter, with minimal non-cancer blood cells left on the filter. The feasibility of the telomerase activity measurement of a single cancer cell taken from the filter after capture was proven. The on-filter and off-filter cultures of the captured cancer cells were also demonstrated

Charged multiplicity density and number of participant nucleons in relativistic nuclear collisions

The energy and centrality dependences of charged particle pseudorapidity density in relativistic nuclear collisions were studied using a hadron and string cascade model, JPCIAE. Both the relativistic $p+\bar p$ experimental data and the PHOBOS and PHENIX $Au+Au$ data at RHIC energy could be fairly reproduced within the framework of JPCIAE model and without retuning the model parameters. The predictions for $Pb+Pb$ collisions at the LHC energy were also given. We computed the participant nucleon distributions using different methods. It was found that the number of participant nucleons is not a well defined variable both experimentally and theoretically. Thus it may be inappropriate to use the charged particle pseudorapidity density per participant pair as a function of the number of participant nucleons for distinguishing various theoretical models. A discussion for the effect of different definitions in nuclear radius (diffused or sharp) was given.Comment: 15 pages, 7 figure